Mills made her screen debut at age 11 weeks in her godfather Noel Coward's acclaimed war picture, "In Which We Serve" (1941). She then appeared alongside her father in 1947's "The October Man" and a couple of other juvenile parts. Her first adult and leading role came with "No, My Darling Daughter" (1961), in which she was the child of Michael Redgrave who falls in love with the son of his business associate. The minor comedy was released a year after Hayley had scored a memorable success in "Pollyanna" and the same year as "The Parent Trap" which firmed the younger actress' status as the ranking screen juvenile of the era. Thus, as Mills tried to forge a career as an ingenue, she remained in the shadows of her father and sister. Her roles in two British low brow comedies, "Carry On Sailor" (1963) and "Carry On Jack" (1964) did not raise her profile. She appeared in "The Rare Breed" (1966) and was among the all-star British cast of "Oh, What a Lovely War" (1969) as a nurse, but remained virtually unknown in America until the TV series. As Hayley matured and her career seemingly waned and Mills became known, she made a second attempt at a film career. Teamed with Jack Lemmon in Billy Wilder's "Avanti!" (1972), she was superb as a somewhat chubby young woman who takes up with an American businessman (Lemmon) in Italy, who turns out to be the son of her mother's lover. In an effort to change her sweet image, Mills gained weight for the role and even appeared nude onscreen. Despite a Golden Globe nomination, she found her film career stalled and she amassed only two more big screen credits: providing a character voice in "Jonathan Living Seagull" (1973) and playing the wife of a recording executive who is pregnant with a demon in "Beyond the Door" (1975).

Although she reprised the role of "Nanny" in the animated ABC special "Nanny and the Professor and the Phantom of the Circus" (1973), Mills worked to shed her lightweight nice image. She was an adulterous wife in "Letters From Three Lovers" (ABC, 1973) and won a Supporting Actress Emmy for her turn as Ben Gazzara's English wife in "QB VII" (ABC, 1977). Other credits include playing a wealthy woman who beds a young stud-for-hire (Leigh McCloskey) in "Alexander: The Other Side of Dawn" (NBC, 1977) and an asylum inmate named Tinkerbell alongside Natalie Wood in "The Cracker Factory" (ABC, 1979). Also in 1979, she appeared in an episode of "The Love Boat" with her father and sister.

After her 1980 marriage to Caulfield, Mills seemed to fade from TV view, whether by her choice or the murmurs resulting from the nature of the marriage. She often worked onstage with Caulfield, notably in "The Elephant Man" and with the short-lived Mirror Repertory Company in New York. Mills had some stage success in England dating from 1955 when she played the tile role in a production of "Alice Through the Looking Glass". Her Broadway debut came in 1959 when she repeated her London stage role in Peter Shaffer's "Five Finger Exercise", for which she earned a Tony nomination. Other credits include Mills playing Wendy in a 1960 London production of "Peter Pan", Gilda in "Alfie" on Broadway in 1964, and the title role of Catherine Sloper in "The Heiress" in London in 1980. In the 90s, she made occasional appearances as a character player in TV-movies like the syndicated "Night of the Fox" (1990) and "A Stranger in the Mirror" (ABC, 1993).